CD83
CD83 is a 45 kDa, type-I membrane glycoprotein belonging to the immunoglobulin superfamily. CD83 is a cell surface marker predominantly expressed on mature dendritic cells (DCs). CD83 is minimally expressed on immature blood DC (BDC) and monocyte derived DC (MoDC). Due to its preferential expression on mature DCs, CD83 is an attractive target for immunotherapy.
Dendritic Cells and the Control of Innate and Adaptive Immune Responses
DCs link the innate and cognate (adaptive) immune systems. Innate immunity is the primary driver of non-specific immune activation in response to foreign agents. Immature DCs specialize in the internalisation of antigens and are distributed throughout peripheral tissues allowing for continuous antigenic surveillance. Termed professional antigen presenting cells (APCs) for their capability to drive primary T cell responses, DCs only require minimal quantities of antigen to initiate immune activation.
Immature DCs are attuned to a variety of signals from infectious and foreign material, which trigger differentiation and maturation (also known as activation) of the DCs. Whilst mature DCs are capable of antigen capture, this activation process reduces the capacity of these cells to internalize antigen, instead up-regulating cytokine release, activation marker expression and processing of antigen for major histocompatibility complex (MHC) presentation. Mature DCs loaded with processed antigen can efficiently recruit T cells, B cells, granulocytes, natural killer (NK) cells, monocytes and other cells of the innate immune system to amplify the response to antigen.
The molecules which become expressed upon DC differentiation and activation aid in linking innate and adaptive immunity. Mature DCs up-regulate the expression of chemokine receptors and adhesion molecules such as CD54, facilitating DC migration to lymph nodes for increased interaction with lymphocytes. Expression of costimulatory molecules, such as CD80 and CD86, provides the requisite co-stimulatory signals for T cell activation and the initiation of an antigen-specific immune response. Ligation of CD40 enhances the expression of co-stimulatory molecules and induces the release of IL-12 to facilitate T cell activation; differentiated T cells then orchestrate the complex interactions of the adaptive immune response.
Since DCs exert control over immune responses, activated DCs can be viewed as a target for intervention across a number of immunological diseases including malignancy and autoimmune diseases.
It will be apparent to the skilled person from the foregoing that compounds that target DCs may modulate the immune response. Accordingly, compounds that bind DCs are desirable, for example, for their therapeutic, prophylactic, diagnostic and prognostic uses.